Esculetin, a Coumarin Derivative, Inhibits Aldose Reductase Activity in vitro and Cataractogenesis in Galactose-Fed Rats

Abstract

Naturally occurring coumarin compounds have received substantial attention due to their pharmaceutical effects. Esculetin is a coumarin derivative and a polyphenol compound that is used in a variety of therapeutic and pharmacological strategies. However, its effect on aldose reductase activity remains poorly understood. In this study, the potential beneficial effects of esculetin on lenticular aldose reductase were investigated in galactose-fed (GAL) rats, an animal model of sugar cataracts. Cataracts were induced in Sprague-Dawley (SD) rats via a 50% galactose diet for 2 weeks, and groups of GAL rats were orally treated with esculetin (10 or 50 mg/kg body weight). In vehicle-treated GAL rats, lens opacification was observed, and swelling and membrane rupture of the lens fiber cells were increased. Additionally, aldose reductase was highly expressed in the lens epithelium and superficial cortical fibers during cataract development in the GAL rats. Esculetin reduced rat lens aldose reductase (RLAR) activity in vitro, and esculetin treatment significantly inhibited lens opacity, as well as morphological alterations, such as swelling, vacuolation and liquefaction of lens fibers, via the inhibition of aldose reductase in the GAL rats. These results indicate that esculetin is a useful treatment for galactose-induced cataracts.

Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

“…For examination of bile duct cell proliferation capacity, we processed immunohistochemical staining for Ki-67 as described previously ( Kim et al ., 2016 ). To perform immunohistochemistry, samples were fixed in 4% paraformaldehyde and then embedded in paraffin.…”

Diosgenin, a Novel Aldose Reductase Inhibitor, Attenuates the Galactosemic Cataract in Rats

“…Subsequently, we performed a strict ARI screening from 224 candidates including 180 natural extracts and 44 nonoriented synthetic compounds and found diosgenin as a potent inhibitor against AR. Diosgenin inhibited the normal rat lens AR in a good dose-dependent manner, and its IC 50 was 4.59 × 10 −6 mol/L, that was on the similar level as other ongoing plant-derived AR inhibitors [ 10 – 12 ].…”

“…AR has higher affinity to galactose than to glucose; the metabolite galactitol is more poorly reduced by SDH than sorbitol, and it takes shorter time to form rat galactosemic cataract model than another one [ 3 , 4 , 18 ]. So, lens osmotic expansion is more predominant in galactosemic cataract than that in diabetic cataract; the former model is more suitable for the investigation of ARIs than the latter [ 9 , 10 , 14 , 19 ]. Therefore, we use galactose instead of glucose to induce the osmotic expansion of LECs and rat galactosemic cataract model in the following assessments.…”

“…Another promising AR inhibitor is Kinostat, which shows strong effects against cataract on diabetic dogs, and may acquire FDA approval in 2017 [ 9 ]. Recently, the plant-derived compounds have also obtained considerable attention; some flavones even show remarkable AR inhibitory activity with IC 50 at 10 −6 mol/L level [ 10 – 12 ]. Here, we report a new-screened ARI, diosgenin, and its effects against sugar cataract in vitro and in vivo.…”

Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation

“…For examination of thyroid cell proliferation, we processed immunohistochemical staining for Ki-67 as described previously ( Kim et al ., 2016 ; Jeong et al ., 2017 ). To perform immunohistochemistry, samples were fixed in 4% paraformaldehyde and then embedded in paraffin.…”